Recent clinical trials have shown that early treatment using the thrombolytic agent, rt-PA, can improve the clinical outcome in certain patients with ischemic stroke. But even when treatment is initiated within the 3 hour "therapeutic window of opportunity", there are few cases that derive significant benefit from rt-PA and some patients may actually deteriorate. The development of more effective treatment options and extension of the therapeutic window to later time points will depend on the ability of clinicians to differentiate patients with ischemic stroke that have the potential to benefit from thrombolysis (or some other therapy) from those that will model to differentiate ischemic brain tissue, prior to reperfusion, with the potential for recovery (i.e. receptive to therapeutic intervention) from irreversibly damaged tissues (i.e. no response or may worsen with thrombolysis) for the purpose of selecting treatment options. Our approach is based on a mechanistic hypothesis that multi-parameter MRI, by accounting for the multiple biophysical states of water in tissue and tissue perfusion, will yield a more complete classification of ischemic brain tissue than any single MRI parameter. A secondary goal of the project will be to define post reperfusion MRI indications of treatment efficacy in terms of successful or unsuccessful reperfusion and the implications for recovery, no change in status or further deterioration of the involved tissue. Based on development of MRI based tissue models to predict ischemic histopathology and eventual outcome during the current funding period, we propose to accomplish these objectives using a multi- parameter MRI data approach in conjunction with sophisticated data analysis routines.